Evidence that the Plant Cannabinoid Cannabigerol is a Highly Potent alpha2-Adrenoceptor Agonist and Moderately Potent 5HT1A Receptor Antagonist
Cannabis is the source of at least seventy phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being D9-tetrahydrocannabinol, cannabidiol and D9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. This investigation has provided the first evidence that cannabigerol can activate alpha2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors.
Immunoactive Effects of Cannabinoids: Considerations for the Therapeutic Use of Cannabinoid Receptor Agonists & Antagonists
The active constituents of Cannabis sativa have been used for centuries as recreational drugs and medicinal agents. Today, marijuana is the most prevalent drug of abuse in the United States and, conversely, therapeutic use of marijuana constituents are gaining mainstream clinical and political acceptance. Given the documented contributions of endocannabinoid signaling to a range of physiological systems, including cognitive function, and the control of eating behaviors, it is unsurprising that cannabinoid receptor agonists and antagonists are showing significant clinical potential. In addition to the neuroactive effects of cannabinoids, an emerging body of data suggests that both endogenous and exogenous cannabinoids are potently immunoactive. The central premise of this review article is that the immunological effects of cannabinoids should be considered in the context of each prescribing decision. We present evidence that the immunological effects of cannabinoid receptor agonists and antagonists are highly relevant to the spectrum of disorders for which cannabinoid therapeutics are currently offered.
Recent advances in understanding of the mode of action of tetrahydrocannabinol and related cannabinoid ingredients of marijuana, plus the accumulating anecdotal reports on potential medical benefits have spurred increasing research into possible medicinal uses of cannabis. Recent clinical trials with smoked and vaporized marijuana, as well as other botanical extracts indicate the likelihood that the cannabinoids can be useful in the management of neuropathic pain, spasticity due to multiple sclerosis, and possibly other indications. As with all medications, benefits and risks need to be weighed in recommending cannabis to patients. We present an algorithm that may be useful to physicians in determining whether cannabis might be recommended as a treatment in jurisdictions where such use is permitted.
Marijuana is classified by the Drug Enforcement Agency (DEA) as an illegal Schedule I drug which has no accepted medical use. However, recent studies have shown that medical marijuana is effective in controlling chronic non-cancer pain, alleviating nausea and vomiting associated with chemotherapy, treating wasting syndrome associated with AIDS, and controlling muscle spasms due to multiple sclerosis. These studies state that the alleviating benefits of marijuana outweigh the negative effects of the drug, and recommend that marijuana be administered to patients who have failed to respond to other therapies. Despite supporting evidence, the DEA refuses to reclassify marijuana as a Schedule II drug, which would allow physicians to prescribe marijuana to suffering patients. The use of medical marijuana has continued to gain support among states, and is currently legal in 16 states and the District of Columbia. This is in stark contrast to the federal government’s stance of zero-tolerance, which has led to a heated legal debate in the United States. After reviewing relevant scientific data and grounding the issue in ethical principles like beneficence and nonmaleficence, there is a strong argument for allowing physicians to prescribe marijuana. Patients have a right to all beneficial treatments and to deny them this right violates their basic human rights.
The New England Journal of Medicine: We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries. A total of 1446 votes were cast from 72 countries and 56 states and provinces in North America, and 118 comments were posted.
The possible medicinal use of cannabinoids for chronic diseases emphasises the need to understand the long-term effects of these compounds on the central nervous system. We provide a quantitative synthesis of empirical research pertaining to the non-acute (residual) effects of cannabis on the neurocognitive performance of adult human subjects.
Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.
Psychotic experiences are linked to Cannabis use in adolescents in the community because of common underlying environmental risk factors
Cannabis users are more likely to have psychotic experiences (PEs). The degree to which these associations are driven by genetic or environmental influences in adolescence is unknown. This study estimated the genetic and environmental contributions to the relationship between cannabis use and PEs. Specific PEs were measured in a community-based twin sample (4830 16-year-old pairs) using self- reports and parent-reports. Adolescents reported on ever using cannabis. Multivariate liability threshold structural equation model-fitting was conducted. Cannabis use was significantly correlated with PEs. Modest heritability (37%), common environmental influences (55%) and unique environment (8%) were found for cannabis use. For PEs, modest heritability (27–54%), unique environmental influences (E1⁄412– 50%) and little common environmental influences (11–20%), with the exception of parent-rated Negative Symptoms (42%), were reported. Environmental influences explained all of the covariation between cannabis use and paranoia, cognitive disorganization and parent-rated negative symptoms (bivariate common environment 1⁄4 69–100%, bivariate unique environment 1⁄4 28–31%), whilst the relationship between cannabis use and hallucinations indicated familial influences. Cannabis use explains 2–5% of variance in positive, cognitive, and negative PEs. Cannabis use and psychotic experience co-occur due to environmental factors. Focus on specific environments may reveal why adolescent cannabis use and psychotic experiences tend to ‘travel together’.
New Mexico was the first state to list post-traumatic stress disorder (PTSD) as a condition for the use of medical cannabis. There are no published studies, other than case reports, of the effects of cannabis on PTSD symptoms. The purpose of the study was to report and statistically analyze psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico Medical Cannabis Program from 2009 to 2011. Methods: The Clinician Administered Posttraumatic Scale for DSM-IV (CAPS) was administered retrospectively and symptom scores were then collected and compared in a retrospective chart review of the first 80 patients evaluated. Results: Greater than 75% reduction in CAPS symptom scores were reported when patients were using cannabis compared to when they were not. Conclusions: Cannabis is associated with reductions in PTSD symptoms in some patients, and prospective, placebo-controlled study is needed to determine efficacy of cannabis and its constituents in treating PTSD.
Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai‘i.